Hydroxy amides of dihydroxy



Patented Mar. 1, 1949 HYDROXY AMIDES OF DIHYDROXY BENZOIC ACID John L.Huck, Jr., Nutley, J., assignor to Hon- 'mann-La Roche Inc., Nutley, N.J., a corpora! tion of New Jersey No Drawing. Application January 31,1948,

Serial No. 5,683

4 Claims. (Cl. 260-559) The present invention relates to aliphatichydroxy amides of gentisic acid and to their method of production. Thenew compounds may be represented by the following formula:

(A) HO GO ONH-X-OH with an aliphatic hydroxy amine of the followinggeneral formula:

The reaction can be represented by the following equation:

600012 NHz-X-OH I OH OOONH-X-OH ROH In Formulae B and D, R stands for analkyl radical such as, for example, methyl, ethyl, propyl and the like,and X in Formulae C and D has the same significance as described forFormula A.

In general, the temperature employed in the reaction may vary over awide range as, for example, from about 50 C. to about 180 C.Temperatures of about 100? C. to about 130 C. are preferably employed.The reaction can readily be carried out on a steam bath. The process canbe carried out in the presence or absence of a solvent. An inert diluentas, for example, benzene, toluene, and the like can be employed. Sincethe esters of 'gentisic acid are relatively unstable, being oxidized byair in alkaline media, it is preferred to carry out the reaction in aninert atmosphere as, for example, in the presence of nitrogen or carbondioxide.

The amounts of the reagents employed may be widely varied. However, ithas been found advantageous to employ the hydroxy aliphatic amine inexcess, since maximum yields of the lower aliphatic hydroxy amides ofgentisic acid are obtained. If less of the hydroxy aliphatic amine isemployed as, for example, in a ratio of 1:1, the yields are somewhatlower. Excess of the amine can be recovered after the reaction iscompleted by distilling it mi from the reaction mixture under vacuum.

The following examples will serve to illustrate the invention:

Example 1 N- Bhydro xyetliyl) -gentisamide H O 168 grams (1 mol) ofmethylgentisate are stirred into 200 cc. of benzene, 244 grams (4 mols)of monoethanolamine are added and heated under stirring to -80 C. in anitrogen atmosphere. The benzol and the methanol formed are distilledoff at the same time. The residue is now heated in a vacuum in order todistill oil the excess of ethanolamine at a bath temperature notsubstantially exceeding 180 0. (preferably at 150 C.). The residue isacidified with hydrochloric acid and allowed to cool forcrystallization. The crystals are sucked off and washed with a smallamount of ice cold water. They can, if necessary, be recrystallized fromwater. The N-(fl-hydroxyethyl)-gentisamide forms white prisms. Thecompound melts at 145-148 C.

Example 2 168 grams of methylgentisate are heated with 92.5 grams (1.5mol) of ethanolamine in a vacuum at a bath temperature of -130 C. foronehour. The resulting solution is acidified and the product allowed tocrystallize. The same product as in Example 1 is obtained.

Example 3 182 grams of ethylgentisate are reacted with 92.5 grams ofethanolamine in the manner de- 3 scribed in Example 2. The productobtained is the same as in Example 1.

Example 4 v N- (B-hydroxypropyl) -gentisamide 168 grams (1 mol) ofmethylgentisate are heated with 115 grams of1,1-dimethyl-2-hydroxyethylamine in a vacuum to 100-110 C. for twohours. The residue is dissolved in hot water and the solution acidifiedwith hydrochloric acid. When allowed to cool, the reaction productcrystallizes in white crystals with a melting point of 1'79- 180 C.

Example 6 N- 13,3 ,8 '-trihydroxy-tertiary-butyl) -gentisamide OHIOHOONH-C-CELOH CHaOH 168 grams (1 mol) of methylgentisate are mixed with181.5 grams of fi,fl,p"-trihydroxytertiary-butylamine and the mixturekept at C. in a nitrogen atmosphere for three hours. The melt isdissolved in hot water and the solution allowed to cool. White crystalsare obtained melting at 191-192 C.

l The above examples, it will be understood, are given by way ofillustration. Those skilled in the art will recognize that other alkylesters of gentisic acid may be reacted with other hydroxy aliphaticamines to form other aliphatic hydroxy amides of gentisic acid whichcome within the scope of the invention.

I claim:

1. A lower alkylolamide of gentisic acid.

2. N- (p-hydroxyethyl) -gentisamide.

3. N-(B-hydroxypropyl) -gentisamide.

4. N-(1,1-dimethyl-fi-hydroxyethyl) -gentisamide.

JOHN L. I-IUCK, JR.

REFERENCES CITED The following references are of record in the

